A Missense Variant in the IKZF2 Gene Identified in a Genetically Undiagnosed Family With Hearing Loss.

Hearing loss is one of the conditions characterized by a high degree of genetic heterogeneity, and whole exome sequencing (WES) serves as a key method for identifying pathogenic variants. To date, 155 genes have been reported to be associated with nonsyndromic hearing loss. Recently, a study by Velde et al.

The role of m5C RNA modification in cancer development and therapy.

RNA modifications have been demonstrated to affect the function, stability, processing, and interactions of RNA, including pseudouridylation, acetylation and methylation. RNA methylation products, such as N6-methyladenosine (m6A), 5-methylcytidine (m5C), N7-methylguanosine (m7G), 2'-O-dimethyladenosine (m6Am), and N1-methyladenosine (m1A), have been reported to participate in tumorigenesis and tumor progression. The role of m6A in carcinogenesis has been well studied and summarized.

Genetic testing in pediatric kidney transplant recipients to promote informed choice and improve individualized monitoring.

Background: The growing body of research on kidney disease in children has identified a broad spectrum of genetic etiologies.

Methods: We conducted a prospective study to evaluate the efficacy of an optimized genetic test and subclinical changes in a real-world context before kidney transplantation. All cases involved recipients under the age of 18 who underwent whole exome sequencing (ES) between 2013 and 2022.

Validating the splicing effect of rare variants in the SLC26A4 gene using minigene assay.

Background: The SLC26A4 gene is the second most common cause of hereditary hearing loss in human. The aim of this study was to utilize the minigene assay in order to identify pathogenic variants of SLC26A4 associated with enlarged vestibular aqueduct (EVA) and hearing loss (HL) in two patients.

Methods: The patients were subjected to multiplex PCR amplification and next-generation sequencing of common deafness genes (including GJB2, SLC26A4, and MT-RNR1), then bioinformatics analysis was performed on the sequencing data to identify candidate pathogenic variants.

Novel Clinical Manifestation and Favorable Treatment Outcome of Cochlear Implant in a Chinese Family With Likely Pathogenic Variant of the P2RX2 Gene.

The rapid development and clinical application of sequencing technologies enable the genetic diagnosis of inherited deafness. P2RX2, as the gene responsible for autosomal dominant non-syndromic deafness-41 (DFNA41), has been proven to be essential for life-long normal hearing and for the protection of noise-induced hearing loss (NIHL). Our present study reports a missense variant in the P2RX2 gene (c.

Comparison of the TNM9th and 8th editions for localized and locally advanced anal squamous cell carcinoma treated nonsurgically and proposal of a new stage grouping system.

Objective: To compare the survival discrimination of the TNM9th and 8th editions for localized and locally advanced anal squamous cell carcinoma (ASCC) treated nonsurgically and suggest a simple revised staging system with data from the Surveillance, Epidemiology, and End Results (SEER) database.

Methods: Overall survival (OS) was the primary endpoint. Survival comparisons between the T and N stages and the different staging systems were performed using the Kaplan-Meier method and log-rank test, followed by correlation analysis and variable importance analysis (VIA).

Unraveling role of ubiquitination in drug resistance of gynecological cancer.

Chemotherapy is the principal treatment for advanced cancer patients. However, chemotherapeutic resistance, an important hallmark of cancer, is considered as a key impediment to effective therapy in cancer patients. Multiple signaling pathways and factors have been underscored to participate in governing drug resistance.

Novel likely pathogenic variant in the EYA1 gene causing Branchio oto renal syndrome and the exploration of pathogenic mechanisms.

Objective: Branchio-oto-renal syndrome (BOR, OMIM#113,650) is a rare autosomal dominant disorder that presents with a variety of symptoms, including hearing loss (sensorineural, conductive, or mixed), structural abnormalities affecting the outer, middle, and inner ear, branchial fistulas or cysts, as well as renal abnormalities.This study aims to identify the pathogenic variants by performing genetic testing on a family with Branchio-oto-renal /Branchio-otic (BO, OMIM#602,588) syndrome using whole-exome sequencing, and to explore possible pathogenic mechanisms.

Methods: The family spans 4 generations and consists of 9 individuals, including 4 affected by the BOR/BO syndrome.

PKHD1L1, a gene involved in the stereocilia coat, causes autosomal recessive nonsyndromic hearing loss.

Identification of genes associated with nonsyndromic hearing loss is a crucial endeavor given the substantial number of individuals who remain without a diagnosis after even the most advanced genetic testing. PKHD1L1 was established as necessary for the formation of the cochlear hair-cell stereociliary coat and causes hearing loss in mice and zebrafish when mutated. We sought to determine if biallelic variants in PKHD1L1 also cause hearing loss in humans.

Novel compound heterozygous pathogenic variants in the SLC3A1 gene in a Chinese family with cystinuria.

Background: Cystinuria is an autosomal recessive disorder characterized by a cystine transport deficiency in the renal tubules due to mutations in two genes: SLC3A1 and SLC7A9. Cystinuria can be classified into three forms based on the genotype: type A, due to mutations in the SLC3A1 gene; type B, due to mutations in the SLC7A9 gene; and type AB, due to mutations in both genes.

Methods: We report a 12-year-old boy from central China with cystine stones.

Phenotypic variability in two female siblings with oocyte maturation arrest due to a TUBB8 variant.

Tubulin beta-8 (TUBB8) is expressed exclusively in the oocyte and early embryo, encoding a beta-tubulin polypeptide that participates in the assembly of microtubules. TUBB8 was first attributed to being responsible for oocyte MI arrest. Further studies have demonstrated that patients with different pathogenic variants have variable phenotypes.

, A Gene Involved in the Stereocilia Coat, Causes Autosomal Recessive Nonsyndromic Hearing Loss.

Identification of genes associated with nonsyndromic hearing loss is a crucial endeavor given the substantial number of individuals who remain without a diagnosis after even the most advanced genetic testing. was established as necessary for the formation of the cochlear hair-cell stereociliary coat and causes hearing loss in mice and zebrafish when mutated. We sought to determine if biallelic variants in also cause hearing loss in humans.

Early prediction of growth patterns after pediatric kidney transplantation based on height-related single-nucleotide polymorphisms.

Background: Growth retardation is a common complication of chronic kidney disease in children, which can be partially relieved after renal transplantation. This study aimed to develop and validate a predictive model for growth patterns of children with end-stage renal disease (ESRD) after kidney transplantation using machine learning algorithms based on genomic and clinical variables.

Methods: A retrospective cohort of 110 children who received kidney transplants between May 2013 and September 2021 at the First Affiliated Hospital of Zhengzhou University were recruited for whole-exome sequencing (WES), and another 39 children who underwent transplant from October 2021 to March 2022 were enrolled for external validation.

[Analysis of phenotype and pathogenic variants in a Chinese pedigree affected with Multiple synostoses syndrome type 1].

Objective: To explore the clinical and genetic characteristics of a Chinese pedigree affected with Multiple synostoses syndrome type 1 (SYNS1).

Methods: Clinical data of the proband and her family members were collected. Genomic DNA was extracted from peripheral blood samples.

[Analysis of clinical phenotype and genetic variants among four Chinese pedigrees affected with Waardenburg syndrome].

Objective: To explore the genetic basis for four Chinese pedigrees affected with Waardenburg syndrome (WS).

Methods: Four WS probands and their pedigree members who had presented at the First Affiliated Hospital of Zhengzhou University between July 2021 and March 2022 were selected as the study subjects. Proband 1, a 2-year-and-11-month female, had blurred speech for over 2 years.

Stage IIB-IVA cervix carcinoma in elderly patients treated with radiation therapy: a longitudinal cohort study by propensity score matching analysis.

Objective: We aimed to evaluate the treatment modality and prognostic impact of the age at diagnosis on stage IIB-IVA cervix carcinoma (CC) patients who received radiotherapy (RT).The evaluation was performed using the Surveillance, Epidemiology, and End Results (SEER) database.

Patients And Methods: From the SEER database, we included the patients with a histopathological diagnosis of CC between 2004 and 2016.

Molecular Mechanisms and Clinical Phenotypes of Missense Variants.

The gene is the most common gene responsible for hearing loss (HL) worldwide, and missense variants are the most abundant type. pathogenic missense variants cause nonsyndromic HL (autosomal recessive and dominant) and syndromic HL combined with skin diseases. However, the mechanism by which these different missense variants cause the different phenotypes is unknown.

Molecular diagnosis of hereditary deafness and application of stepwise testing strategy.

Hereditary deafness is one of the most common sensory disorders in humans, and exhibits high genetic heterogeneity. At present, the commonly used molecular diagnostic methods include gene chip, Sanger sequencing, targeted enrichment sequencing, and whole-exome sequencing, with diagnosis rates reaching 33.5%-56.

Development and validation of a radiomics-based nomogram for the prediction of postoperative malnutrition in stage IB1-IIA2 cervical carcinoma.

Objective: In individuals with stage IB1-IIA2 cervical cancer (CC) who received postoperative radiotherapy ± chemotherapy (PORT/CRT), the interaction between sarcopenia and malnutrition remains elusive, let alone employing a nomogram model based on radiomic features of psoas extracted at the level of the third lumbar vertebra (L3). This study was set to develop a radiomics-based nomogram model to predict malnutrition as per the Patient-Generated Subjective Global Assessment (PG-SGA) for individuals with CC.

Methods: In total, 120 individuals with CC underwent computed tomography (CT) scans before PORT/CRT.

Increased diagnostic yield in a cohort of hearing loss families using a comprehensive stepwise strategy of molecular testing.

Hearing loss is one of the most common sensory disorders in humans. This study proposes a stepwise strategy of deafness gene detection using multiplex PCR combined with high-throughput sequencing, Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), and whole-exome sequencing (WES) to explore its application in molecular diagnosis of hearing loss families. A total of 152 families with hearing loss were included in this study, the highest overall diagnosis rate was 73% (111/152).

A 5-year survival status prognosis of nonmetastatic cervical cancer patients through machine learning algorithms.

Background: Prediction models with high accuracy rates for nonmetastatic cervical cancer (CC) patients are limited. This study aimed to construct and compare predictive models on the basis of machine learning (ML) algorithms for predicting the 5-year survival status of CC patients through using the Surveillance, Epidemiology, and End Results public database of the National Cancer Institute.

Methods: The data registered from 2004 to 2016 were extracted and randomly divided into training and validation cohorts (8:2).

Case report: Clinical and genetic analysis of a family with nonsyndromic auditory neuropathy.

Background: Auditory neuropathy (AN) is a hearing disorder caused by the failure of inner hair cells, auditory nerve synapses and/or auditory nerves. With the development of high-throughput sequencing technology, the genetic factors of AN have been revealed, and genetic testing has become an important tool for identifying different types of AN.

Case Description: To study the genetic cause of nonsyndromic auditory neuropathy in a Chinese family.

Impact of marital status on overall survival in patients with early-stage hepatocellular carcinoma.

The purpose of the present research was to assess the prognostic impact of marital status in hepatocellular carcinoma (HCC) patients with tumors ≤ 2 cm (stage Ia) based on the data from the Surveillance, Epidemiology, and End Results (SEER) database. Patients who received a histopathologic HCC diagnosis between 2004 and 2016 were recruited. Overall survival (OS) was the major outcome measure.

Defining the sensitivity landscape of EGFR variants to tyrosine kinase inhibitors.

Tyrosine kinase inhibitor (TKI) is a standard treatment for patients with NSCLC harboring constitutively active epidermal growth factor receptor (EGFR) mutations. However, most rare EGFR mutations lack treatment regimens except for the well-studied ones. We constructed two EGFR variant libraries containing substitutions, deletions, or insertions using the saturation mutagenesis method.

A likely pathogenic POLD1 variant associated with mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome in a Chinese patient.

Background: Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL; OMIM# 615381) is a rare autosomal dominant disorder, with only a few reported cases worldwide. Herein, we describe the clinical features and underlying molecular etiology of MDPL syndrome in an 8-year-old Chinese patient.

Methods: We performed otological, endocrine, ultrasound, and radiological examinations, as well as genetic testing.